Hormone Binding to the Follicle-Stimulating Hormone Receptor - Crystal Clear!

Abstract

The receptors for the trophic hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyrotropin (TSH) play a central role in endocrinology. These receptors face the challenge to accommodate large heterodimeric glycoprotein ligands within their extracellular hormone-binding domain. Until recently, the mechanism of hormone binding and consequently the mode of receptor activation remained enigmatic. By solving the crystal structure of human follicle-stimulating hormone bound to the receptor's hormone binding domain, it has become clear that the follicle-stimulating hormone receptor grabs the glycoprotein hormone in a hand-clasp mode resulting in a hormone orientation perpendicular to the long axis of the ligand-binding domain. These findings have important ramifications for our understanding of the molecular mechanism of receptor activation and may provide a rational basis for the development of small, non-peptidic FSH receptor ligands.

Key words

Crystal structure - follicle-stimulating hormone - glycoprotein hormones - G proteins

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